New therapeutic combinations for the treatment of Progressive Fibrosing interstitial lung diseases

Abstract

The invention concerns an oral pharmaceutical composition comprising either 18 mg or 9 mg of the PDE4B-inhibitor of formula III a therapeutically effective dose of a second active agent selected from the group consisting of nintedanib or pirfenidone and optionally, one or more pharmaceutically acceptable carriers or excipients for the treatment of a patient suffering from a progressive fibrosing interstitial lung disease (PF-ILD), wherein this oral pharmaceutical composition is to be administered to said patient twice daily. The invention further concerns the use of the PDE4B-inhibitor of formula III for preparing an oral pharmaceutical composition comprising either 18 mg or 9 mg of the PDE4B-inhibitor of formula III for use in a method of treating a patient suffering from one or more Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs), wherein said oral pharmaceutical composition is to be orally administered twice daily to said patient in combination with a therapeutically effective amount of a therapeutically effective dose of a second active agent selected from the group consisting of nintdanib and pirfenidone.

1 - 13 . (canceled) 
     
     
         14 . A method of treating one or more Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs), comprising the step of administering orally to a patient in need thereof 18 mg of the PDE4B-inhibitor of formula III 
       
         
           
           
               
               
           
         
       
       twice daily in combination with a therapeutically effective amount of pirfenidone. 
     
     
         15 . The method according to  claim 14 , wherein pirfenidone is administered in a dose and dose regimen as authorized for pirfenidone. 
     
     
         16 . The method according to  claim 14 , wherein pirfenidone is administered in a dose and dose regimen leading to a daily dose between 801 mg and 2403 mg. 
     
     
         17 . The method according to  claim 14 , wherein the 18 mg of the PDE4B-inhibitor of formula III is administered to the patient in need thereof twice daily in one oral pharmaceutical composition and wherein the therapeutically effective amount of pirfenidone is administered to said patient in need thereof in a separate oral pharmaceutical composition. 
     
     
         18 . The method according to  claim 14 , wherein the 18 mg of the PDE4B-inhibitor of formula III and the therapeutically effective amount of pirfenidone are administered together in the same oral pharmaceutical composition twice daily to the patient in need thereof. 
     
     
         19 . A method of treating idiopathic pulmonary fibrosis (IPF), comprising the step of administering orally to a patient in need thereof 18 mg of the PDE4B-inhibitor of formula III 
       
         
           
           
               
               
           
         
       
       twice daily in combination with a therapeutically effective amount of pirfenidone. 
     
     
         20 . The method according to  claim 19 , wherein pirfenidone is administered in a dose and dose regimen as authorized for pirfenidone. 
     
     
         21 . The method according to  claim 19 , wherein pirfenidone is administered in a dose and dose regimen leading to a daily dose between 801 mg and 2403 mg. 
     
     
         22 . The method according to  claim 19 , wherein the 18 mg of the PDE4B-inhibitor of formula III is administered to the patient in need thereof twice daily in one oral pharmaceutical composition and wherein the therapeutically effective amount of pirfenidone is administered to said patient in need thereof in a separate oral pharmaceutical composition. 
     
     
         23 . The method according to  claim 19 , wherein the 18 mg of the PDE4B-inhibitor of formula III and the therapeutically effective amount of pirfenidone are administered together in the same oral pharmaceutical composition twice daily to the patient in need thereof. 
     
     
         24 . A method of treating one or more Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs), comprising the step of administering orally to a patient in need thereof 18 mg of the PDE4B-inhibitor of formula III 
       
         
           
           
               
               
           
         
       
       twice daily in combination with a therapeutically effective amount of nintedanib. 
     
     
         25 . The method according to  claim 24 , wherein the therapeutically effective amount of nintedanib is 150 mg twice daily. 
     
     
         26 . The method according to  claim 24 , wherein the therapeutically effective amount of nintedanib is 100 mg twice daily. 
     
     
         27 . The method according to  claim 24 , wherein the 18 mg of the PDE4B-inhibitor of formula III is administered to the patient in need thereof twice daily in one oral pharmaceutical composition and wherein the therapeutically effective amount of nintedanib is administered to said patient in need thereof in a separate oral pharmaceutical composition. 
     
     
         28 . The method according to  claim 24 , wherein the 18 mg of the PDE4B-inhibitor of formula III and the therapeutically effective amount of nintedanib are administered together in the same oral pharmaceutical composition twice daily to the patient in need thereof. 
     
     
         29 . A method of treating idiopathic pulmonary fibrosis (IPF), comprising the step of administering orally to a patient in need thereof 18 mg of the PDE4B-inhibitor of formula III 
       
         
           
           
               
               
           
         
       
       twice daily in combination with a therapeutically effective amount of nintedanib. 
     
     
         30 . The method according to  claim 29 , wherein the therapeutically effective amount of nintedanib is 150 mg twice daily. 
     
     
         31 . The method according to  claim 29 , wherein the therapeutically effective amount of nintedanib is 100 mg twice daily. 
     
     
         32 . The method according to  claim 29 , wherein the 18 mg of the PDE4B-inhibitor of formula III is administered to the patient in need thereof twice daily in one oral pharmaceutical composition and wherein the therapeutically effective amount of nintedanib is administered to said patient in need thereof in a separate oral pharmaceutical composition. 
     
     
         33 . The method according to  claim 29 , wherein the 18 mg of the PDE4B-inhibitor of formula III and the therapeutically effective amount of nintedanib are administered together in the same oral pharmaceutical composition twice daily to the patient in need thereof.